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PMID: 8246981 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Hydrolysis of phosphatidylcholine couples Ras to activation of Raf protein kinase during mitogenic signal transduction.

Molecular and cellular biology ·Vol. 13 ·No. 12 ·1993-12-00 ·Pages 7645-51

Cai H, Erhardt P, Troppmair J, Diaz-Meco MT, Sithanandam G, Rapp UR, Moscat J, Cooper GM

Abstract

We have investigated the relationship between hydrolysis of phosphatidylcholine (PC) and activation of the Raf-1 protein kinase in Ras-mediated transduction of mitogenic signals. As previously reported, cotransfection of a PC-specific phospholipase C (PC-PLC) expression plasmid bypassed the block to cell proliferation resulting from expression of the dominant inhibitory mutant Ras N-17. In contrast, PC-PLC failed to bypass the inhibitory effect of dominant negative Raf mutants, suggesting that PC-PLC functions downstream of Ras but upstream of Raf. Consistent with this hypothesis, treatment of quiescent cells with exogenous PC-PLC induced Raf activation, even when normal Ras function was blocked by Ras N-17 expression. Further, activation of Raf in response to mitogenic growth factors was blocked by inhibition of endogenous PC-PLC. Taken together, these results indicate that hydrolysis of PC mediates Raf activation in response to mitogenic growth factors.

MeSH Terms
3T3 Cells Animals Cell Division Enzyme Activation Genes, ras Hydrolysis Mice Mutation Phosphatidylcholines/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-raf Signal Transduction Transfection Type C Phospholipases/antagonists & inhibitors,metabolism
Chemicals
Phosphatidylcholines Proto-Oncogene Proteins Proto-Oncogene Proteins c-raf Type C Phospholipases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Cai H
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Erhardt P
Troppmair J
Diaz-Meco M T
Sithanandam G
Rapp U R
Moscat J
Cooper G M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.12.7645-7651.1993
Published
1993-12-00
Pages
7645-51
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC364836
Subset
IM
Grants
NCI NIH HHS · R01 CA18689 · United States
External Links
PubMed source DOI: 10.1128/mcb.13.12.7645-7651.1993 PMC Full Text View journal details
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